The source of cell-free mitochondrial DNA in trauma and potential therapeutic strategies

Kabilan Thurairajah, Gabrielle Daisy Briggs, Zsolt Janos Balogh, Kabilan Thurairajah, Gabrielle Daisy Briggs, Zsolt Janos Balogh

Abstract

Mitochondria play a key role in the pathophysiology of post-injury inflammation. Cell-free mitochondrial DNA (cf-mtDNA) is now understood to catalyse sterile inflammation after trauma. Observations in trauma cohorts have identified high cf-mtDNA in patients with systemic inflammatory response syndrome and multiple organ failure as well as following major surgery. The source of cf-mtDNA can be various cells affected by mechanical and hypoxic injury (passive mechanism) or induced by inflammatory mechanisms (active mechanism). Multiple forms of cf-mtDNA exist; mtDNA fragments, mtDNA in microparticles/vesicles and cell-free mitochondria. Trauma to cells that are rich in mitochondria are believed to release more cf-mtDNA. This review describes the current understanding of the mechanisms of cf-mtDNA release, its systemic effects and the potential therapeutic implications related to its modification. Although current understanding is insufficient to change trauma management, focussed research goals have been identified to pave the way for monitoring and manipulation of cf-mtDNA release and effects in trauma.

Keywords: Inflammation; MtDNA; Therapeutics; Trauma.

Conflict of interest statement

Conflict of interest

Kabilan Thurairajah, Gabrielle Briggs and Zsolt Balogh declare that they have no conflict of interest.

Ethical statement

An approval by an ethics committee was not applicable. All authors declare that this submission has not been published elsewhere.

Figures

Fig. 1
Fig. 1
Cell-free mitochondrial DNA in trauma. This figure shows the cellular response to tissue injury. a In the immediate area of injury, cf-mtDNA is release from injured cells. b Transport of cf-mtDNA occurs through circulation to remote areas resulting in end-organ injury. c Platelet concentrate infusions contain activated platelets with cf-mtDNA and increase the cf-mtDNA load. d Generation of ATP, ROS in combination with release of mitochondrial DAMPs activate immune cells and platelets to release inflammatory cytokines

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